The principal objective of this application is to understand the genetic basis of the variability in amino acid sequence of immunoglobulin peptide chains and to elucidate at the molecular level the cellular events involved in the synthesis and localization of messenger RNA for immunoglobulins, and the regulation of immunoglobulin synthesis in myeloma cells. Previous work on RNA/DNA hybridization to estimate the number of immunoglobulin genes will be continued with the aim of obtaining a fragment of mRNA coding predominantly for the V region to be used in these experiments. This will allow a better measurement of the number of genes coding for VK in the mouse. Other experiments are designed to determine the time of synthesis of mRNA for immunoglobulins in the cell cycle. Myeloma cells synchronized by double thymidine block will be used; we have previously shown in one myeloma line that immunoglobulin is synthesized at a rather constant rate throughout the cell cycle. Finally, immunoglobulin synthesis on free and membrane-bound ribosomes will be investigated. Synthesis of immunoglobulin on free polysomes has been previously reported by us; the immunoglobulin synthesized will be characterized to establish whether a precursor molecule is synthesized by these polysomes. The mechanism of attachment of ribosomes to membranes and the localization of specific mRNA's on membrane-bound ribosomes will also be studied.